Oral treatment of companion animals with ectoparasiticidal spinosyns

ABSTRACT

The invention provides single-dose oral formulations for controlling an ectoparasite infestation on a companion animal for a prolonged time, said formulations comprising a spinosyn component, or a physiologically acceptable derivative or salt thereof, and a carrier in oral dosage form. It also provides methods for controlling such infestations comprising orally administering a single dose of these formulations to the animal.

This application claims the benefit of provisional application No.60/148,618 filed Aug. 12, 1999.

Companion animals, including but not limited to dogs, cats, and horses,are an increasingly important part of today's society. They providepleasure and companionship to human friends, which leads to what hasbeen termed the human-animal bond. Unfortunately, a number of insectpests and parasites can infest or infect these animals. Such pestsinclude, for example, fleas, lice, mosquitoes, mites, ticks and certainfly species. Safe, effective ways to eliminate these pests are desired,both for the animal's well-being and for the comfort of its humanassociate.

The most common ectoparasites of cats and dogs world-wide are the catand dog fleas, Ctenocephalides felis felis and Ctenocephalides canis,respectively. Interestingly, the cat flea very commonly infests dogs.Fleas annoy the animal it infests and the pet's owner. Frequently, fleascause more serious problems by inducing flea-allergy dermatitis. It hasbeen estimated that flea-related diseases account for over 50% of thedermatological cases reported to veterinarians [D. E. Bevier-Tournay,“Flea and Flea Control” Curr. Vet. Therapy 10: 586-592 (1989)]. Inaddition, the cat flea is known to transmit tapeworms in dogs and hasbeen implicated in the transmission of cat scratch disease and murinetyphus. Other pests of companion animals, such as ticks and mosquitoes,are also known to transmit disease. For example, ticks are known totransmit bacterial and viral diseases; and mosquitoes can infect dogsand cats with the filarial nematode that causes heartworm disease.

Furthermore, economic expenses involved in flea control are high. In theUnited States, for example, pet owners spend over $1 billion dollars forflea control products annually [R. Conniff, “When It Comes to PeskyFlea, Ignorance is Bliss,” Smithsonian: 26: 76-85 (1995)].

Treatments currently available achieve varying degrees of success. Mosttreatments involve chemicals applied to indoor and outdoor surfaces, aswell as to the pet. The chemicals used include a variety of carbamates,organophosphates, pyrethrins and pyrethroids. These compounds often havetoxic side effects that are a problem for both the pet and its owner.For example, concentrated forms of pyrethroids available for use on dogsare extremely toxic and lethal to cats and thus cannot and should not beused on cats. In addition, there is evidence that the use of thesechemicals has led to multiple category insecticide resistance [N. K.Rust and M. W. Dryden, Ann. Rev. Entomol. 42: 451-473 (1997)]. Thus,there continues to be a need for relatively safe, effective agents forcontrolling ectoparasites on companion animals, such as cat and dogfleas.

The spinosyns (also known as A83453 factors) are agriculturalinsecticides that have shown activity against southern armyworm andother insects in the order Lepidoptera, and cotton aphid and othermembers of the order Homoptera. (See, for example, U.S. Pat. No.5,571,901).

The spinosyns were also known to have some ectoparasiticidal activity,i.e., they had in vitro activity against mosquito larvae, black blowflylarvae and adult stable flies, which are members of the insect orderDiptera, and transient systemic activity against larval blowfly andadult stable fly in guinea pigs and sheep (see U.S. Pat. No. 5,571,901,col 26-32). Although it was suggested that the spinosyns would be activeagainst a number of ectoparasites in a number of animals by a variety ofroutes, there have been no subsequently reported studies to supportthese suggestions.

This invention came about by the discovery that spinosyns, such asspinosyn A, can provide prolonged residual control of an ectoparasiteinfestation on a companion animal when a single dose of a spinosyn isadministered orally to the animal. Thus, the invention provides a methodfor prolonged control of the ectoparasite in a safer manner than thatachieved with previously known treatments.

In one aspect, this invention relates to a long-acting, single-dose oralformulation for controlling an ectoparasite infestation on a companionanimal, said formulation comprising an ectoparasiticidal amount of aspinosyn, or a physiologically acceptable derivative or salt thereof,and a physiologically acceptable carrier, in an oral dosage form.

In another aspect the invention relates to the use of a single,long-acting oral formulation of a spinosyn, or a physiologicallyacceptable derivative or salt thereof, for controlling an ectoparasiteinfestation on a companion animal.

It also relates to the use of a spinosyn, or a physiologicallyacceptable derivative or salt thereof, for the manufacture of along-acting single-dose oral medicament for controlling an ectoparasiteinfestation on a companion animal.

This invention also relates to a method of controlling an ectoparasiteinfestation on a companion animal for a prolonged time, comprisingorally administering a single dose of an effective amount of a spinosyn,or a physiologically acceptable derivative or salt thereof, to theanimal. An especially useful method of this invention is a method forcontrolling cat or dog fleas on a companion animal for a prolonged timecomprising orally administering a single dose of an effective amount ofa spinosyn, or a physiologically acceptable derivative or salt thereof,to the animal.

The invention further relates to an article of manufacture, comprisingpackaging material and a formulation for controlling an ectoparasiteinfestation on a companion animal contained within said packagingmaterial, wherein said formulation comprises

an oral long-acting unit dose of an ectoparasiticidal amount of aspinosyn, or a physiologically acceptable derivative or salt thereof,and

a physiologically acceptable carrier; and

wherein said packaging material comprises a label or package insert withinstructions for orally administering the dose to the animal.

This article of manufacture or kit is particularly appropriate when thecompanion animal is a dog or a cat. When the animal is a dog, theformulation contained in the packaging material will generally be intablet form, and the label or package insert will indicate the number oftablets to be given by mouth to the dog and the timing of suchadministration. The timing of doses will generally be every 30 days.When the animal is a cat, the formulation contained in the packagingmaterial will generally be a liquid formulation and the label or packageinsert will indicate the unit dose to be given by mouth to the cat. Thetiming of doses will generally be every 30 days. The contents of eachkit would typically be sufficient to control the ectoparasiteinfestation for a period of several months.

Spinosyns are naturally derived fermentation products. They aremacrolides produced by cultivation of Saccharopolyspora spinosa. Thefermentation produces many factors, including spinosyn A and spinosyn D(also called A83543A and A8354D). Spinosyn A and spinosyn D are the twospinosyns that are most active as insecticides. A product comprisedmainly of these two spinosyns is available commercially under the tradename “spinosad”. The major spinosyn factor, spinosyn A, is known to havean excellent human and animal safety and toxicological profile.

Each spinosyn has a 12-membered macrocyclic ring that is part of anunusual tetracyclic ring system to which two different sugars areattached, the amino-sugar forosamine and the neutral sugar2N,3N,4N-(tri-O-methyl)rhamnose. This unique structure sets thespinosyns apart from other macrocyclic compounds.

Spinosyn A was the first spinosyn isolated and identified from thefermentation broth of Saccharopolyspora spinosa. Subsequent examinationof the fermentation broth revealed that S. spinosa produced a number ofspinosyns that have been called spinosyns A to J (A83543A to J). Theprimary components are spinosyns A and D. Additional spinosyns, letteredfrom K to W, have been identified from mutant strains of S. spinosa. Thevarious spinosyns are characterized by differences in the substitutionpatterns on the amino group of the forosamine, at selected sites on thetetracyclic ring system and on the 2N,3N,4N-(tri-O-methyl)rhamnosegroup.

The term “spinosyn or a derivative thereof” as used herein refers to anindividual spinosyn factor (spinosyn A, B, C, D, E, F, G, H, J, K, L, M,N, O, P, Q, R, S, T, U, V, W or Y), an N-dernethyl derivative of anindividual spinosyn factor, or a combination thereof. For convenience,the term “spinosyn component” will also be used herein to mean anindividual spinosyn, or a physiologically acceptable derivative or saltthereof, or a combination thereof.

Boeck et al. described spinosyns A-H and J (which they called A83543factors A, B, C, D, E, F, G, H and J), and salts thereof, in U.S. Pat.Nos. 5,362,634 (issued Nov. 8, 1994); 5,496,932 (issued March 5, 1996);and 5,571,901 (issued Nov. 5, 1996). Mynderse et al. described spinosynsL-N (which they called A83543 factors L, M and N), their N-demethylderivatives, and salts thereof, in U.S. Pat. No. 5,202,242 (issued Apr.13, 1993); and Turner et al. described spinosyns Q-T (which they calledA83543 factors Q, R, S and T), their N-demethyl derivatives, and saltsthereof, in U.S. Pat. Nos. 5,591,606 (issued Jan. 7, 1997) and 5,631,155(issued May 29, 1997). Spinosyns K, O, P, U, V, W and Y are described,for example, by Carl V. DeAmicis, James E. Dripps, Chris J. Hatton andLaura I. Karr in American Chemical Society's Symposium Series:Phytochemicals for Pest Control, Chapter 11, “Physical and BiologicalProperties of Spinosyns: Novel Macrolide Pest-Control Agents fromFermentation”, pages 146-154 (1997).

The spinosyns can react to form salts that are also useful in themethods and formulations of this invention. The salts are prepared usingstandard procedures for salt preparation. For example, spinosyn A can beneutralized with an appropriate acid to form an acid addition salt. Theacid addition salts of spinosyns are particularly useful. Representativesuitable acid addition salts include salts formed by reaction witheither an organic or inorganic acid such as, for example, sulfuric,hydrochloric, phosphoric, acetic, succinic, citric, lactic, maleic,fumaric, cholic, pamoic, mucic, glutamic, camphoric, glutaric, glycolic,phthalic, tartaric, formic, lauric, stearic, salicylic, methanesulfonic,benzenesulfonic, sorbic, picric, benzoic, cinnamic and like acids.

Using oral formulations of spinosyns to systemically controlectoparasites of companion animals, as a single treatment modality or incombination with other commonly used ectoparasiticidal compounds, hasseveral advantages. Spinosad is a naturally derived fermentation productwith an excellent human and animal safety profile, which is in contrastto currently used synthetic organically derived compounds such assynthetic organophosphates, pyrethroids and pyrethrins, organochlorines,and carbamates. For example, some of the currently used products such asorganophosphates and synthetic pyrethroids are very toxic to cats andcan be lethal.

Spinosyns also provide advantages because they are very effectiveagainst fleas, mites, ticks, lice and flies with post-treatment residualprotection, depending on the dosages used. Furthermore, spinosyns haveno cross-resistance to existing compounds. Thus, they are especiallyuseful against parasite populations on companion animals that haveexisting levels of resistance to currently used products. Spinosyns,therefore, can be used in integrated pest management (IPM) programs toextend the life line of commonly used products where resistance is notwell developed or has not yet developed.

Systemic efficacy (ingestion of blood containing spinosad by the bloodfeeding parasites, such as fleas) provides different mode of exposurecompared to topically applied ectoparasiticides where contact with theparasite at the skin surface is the mode of exposure. The advantages oforal systemic treatments and killing of parasites from ingestion ofblood, compared to topical applications and contact killing, include:

a) reduced exposure to the human applicator and children and objects inthe animal's environment (e.g., flooring, carpets, furniture);

b) no worry about loss from exposure of the animal to water (lakes,streams, bathing, etc.) or from loss due to rubbing;

c) no concern about UV exposure and degradation;

d) no problems with oxidation from oils on skin, etc.; and

e) assurance that the entire dose is administered (compared to a topicalapplication where some of the dose may drip off, rub off and/or remainin the dispensing tube immediately after treatment).

The formulations of this invention may further include, in combinationwith the spinosyn component, one or more other compounds that haveactivity against the specific ectoparasite or endoparasite to becontrolled, such as, for example, synthetic pyrethroids, naturalpyrethins, organophosphates, organochlorines, carbamates, foramidines,avermectins, milbemycins, insect growth regulators (including chitinsynthesis inhibitors, juvenile hormone analogs, and juvenile hormones),nitromethylenes, pyridines and pyrazoles.

All ratios, percentages, and parts discussed herein are “by weight”unless otherwise specified.

The term “oral formulation” means that the spinosyn component orcomponents, either alone or in combination with one or more of the othertypes of compounds listed supra, is formulated into a product orformulation suitable for administering to the animal by mouth. Theseproducts or formulations include, but are not limited to, tablets,capsules, liquids, gels, pastes, oral sprays, buccal formulations,powders and chewable treats or animal feeds containing the activecomponent or components. Generally, such formulations include aphysiologically acceptable carrier. Such carriers are well known in theveterinary arts. Animal feeds are particularly useful carriers.

The term “controlling an ectoparasite infestation” refers to preventing,minimizing or eliminating an infestation by an ectoparasite. The term“ectoparasite” refers to insect and acarine pests that commonly infestor infect companion animals. Examples of such ectoparasites include theegg, larval, pupal, nymphal and adult stages of fleas, lice, mosquitoes,mites, ticks and blood-sucking, biting or nuisance fly species.

The term “companion animals” includes dogs, cats, horses, rabbits andother pets owned and maintained in close association with humans as partof the human-animal bond.

The term “single-dose formulation” means that one dose of theformulation effectively controls the ectoparasite infestation for aprolonged time. The term “prolonged time” comprises a period of at least7 days, preferably a period of at least two weeks. The term“long-acting” means that the activity lasts for a prolonged time.

The methods of this invention are carried out by orally administeringthe spinosyn component to the companion animal. Oral administration maybe carried out using tablets and animal feeds. For some animals, such ascertain cats, administration is best accomplished by using an acceptableliquid formulation that is administered directly or added to their foodration. Especially useful methods of orally administering the spinosyncomponent are by administering it in chewable tablets or treats andanimal feeds.

Conventional oral tablets generally consist of the spinosyn component, adiluent to assist in increasing the powder mass to a convenient size andimprove compressibility, a binder to hold the compressed powder togetherand a lubricant to assist in densification and ejection from the tabletdie. They may also contain a disintegrate to improve disintegration anddissolution as well as stabilizers, colors and flavors. Tablets areoften coated to improve appearance or taste or to alter the dissolutionproperties. Tablets can be designed to dissolve fast or slow, anddepending on the actual volume and compressibility of the drug, large orsmall. They can be made chewable or to dissolve under the tongue or inthe pouch of the cheek.

Conventional liquid formulations for oral administration are usuallysolutions, suspension or emulsions of the spinosyn component togetherwith suitable diluents, solvents, flavors and colors to make a palatabledosage form. Other materials to complex, adjust pH, and improve mouthfeel are also often used.

In carrying out the methods of this invention, an effective amount of aspinosyn, or a physiologically acceptable derivative or salt thereof, isadministered orally to the companion animal. The terms “effectiveamount” and “ectoparasiticidal amount” refer to the amount needed tocontrol the particular ectoparasite infestation. As those in the artwill understand, this amount will vary depending upon a number offactors. These factors include, for example, the type of companionanimal being treated, its weight and general physical condition and thetype of ectoparasite to be controlled.

In general, an effective amount refers to a dose of from about 1 toabout 100 mg of the spinosyn/kg of body weight of the companion animal.More commonly, the effective amount is from about 10 to about 50 mg/kgof body weight of the animal.

Tablet formulations will typically contain from about 1 to about 75percent of spinosyn component or components (by weight) in the tablet.Animal feeds will typically contain from about 0.1 to about 10 percentof spinosyn component or components (by weight) in the feed.

The following examples illustrate the methods of this invention:

EXAMPLE 1 Efficacy of Spinosad Administered per os to Dogs for theTreatment and Control of Ctenocephalides felis

Methods: Nine random-source dogs of both sexes and various ages wereused in this study. The dogs were housed individually inconcrete-floored chain-link runs during the study period and were fed acommerical dry dog food ration with ad libitum access to water. The dogswere allocated to each of the 3 treatment groups (3 dogs per group)based on their pre-treatment flea counts from experimental infestations.

Each dog received one or more gelatin capsules containing technicalactive spinosad powder by mouth. They were dosed at either 50 or 100mg/kg body weight on day 0. Each dog was fed approximately one-half canof moist dog food just prior to and just after receiving theirindividual doses. Each dog was experimentally infested with ˜100 unfedadult fleas on test days −1, 0, 6, 13, 20, 27, 34, 41, and 48. Combcounts for live adult fleas were conducted ˜24 hours following each ofthe subsequent experimental infestations, i.e., on test days 0 (8 hourspost-treatment), 1, 7, 14, 21, 28, 35,42 and 49.

Results: Geometric Mean Percent reduction in live adult flea countscompared to untreated control group in dogs treated orally with spinosadare listed below in Table 1.

TABLE 1 Geometric Mean Percent Reduction in Live Adult Flea Counts inDogs Treated With Spinosad Compared to Untreated Control Group Dose ofSpino- Days Post-treatment sad 8 hrs D1 D7 D14 D21 D28 D35 D42 D49  5097.4 100 99.3 99.7 99.5 95.0 78.1 69.9 ND^(a) mg/kg 100 98.9 100 100 10099.5 99.7 99.4 97.5 94. mg/kg ^(a)ND: not determined

No adverse reactions were seen.

EXAMPLE 2 Efficacy of Spinosad Administered per os to Dogs for theTreatment and Control of Brown Dog Ticks (Rhipicephalus sanguineus) andCat Fleas (Ctenocephalides felis)

Methods: Twelve random-source dogs of both sexes and various ages wereused in the study. The dogs were housed, fed, and watered as inExample 1. The dogs were allocated to each of the 3 treatment groups (4dogs per group) based on their pre-treatment tick counts fromexperimental infestations. Each dog received by mouth one or moregelatin capsules containing either nothing (control) or technical activespinosad powder. The spinosad-treated groups were dosed at either 50 or100 mg/kg body weight on day 0. Each dog was fed approximately one-halfcan of moist dog food just prior to and just after receiving theirindividual capsules. Each dog was infested with ˜50 unfed adult ticks ontest days —1, 7, 14, 21 and 28. Each dog was also concurrently infestedwith ˜100 unfed adult fleas on test days −1, 7, 14, 21, 28, 35 and 42.Comb counts for live adult fleas and ticks were conducted ˜48 hoursfollowing each of the experimental infestations (i.e., on test day 1)and on post-treatment days 9, 16, 23 and 30 for both ticks and fleas andadditionally on days 37 and 44 (for fleas only).

Results: Geometric Mean Percent reduction in live adult flea countscompared to untreated control group in dogs treated orally with spinosadare listed below in Table 2.

TABLE 2 Geometric Mean Percent Reduction in Live Adult Flea Counts inDogs Treated with Spinosad Compared to Untreated Control Group Dose ofDays Post-treatment Spinosad 1 9 16 23 30 37 44  50 mg/kg 100 100 99.7598.3 92.5 93.6 63.1 100 mg/kg 100 100 100 100 100 98.9 97.3

Geometric Mean Percent reductions in live adult tick counts compared tountreated control group in dogs treated orally with spinosad are listedin Table 3.

TABLE 3 Geometric Mean Percent Reduction in Live Adult Tick Counts inDogs Treated with Spinosad Compared to Uutreated Control Group DaysPost-treatment Dose of Spinosad 1 9 16 23 30  50 mg/kg 94.8 67.8 49.152.1 5.0 100 mg/kg 97.2 91.5 70.6 79.7 71.3

Summary of Results (both examples): Orally administered spinosad wasable to provide excellent immediate knockdown and long termpost-treatment residual control of fleas on dogs. The 50 mg/kg doseprovided greater than 90% flea efficacy through day 37 of the study. The100 mg/kg dose provided greater than 90% flea efficacy through day 49 ofthe study (when the study was terminated).

Orally administered spinosad also was able to provide excellentimmediate knockdown and a moderate length of post-treatment residualcontrol of ticks on dogs. The 50 mg/kg dose provided greater than 90%tick efficacy through day 1 of the study. The 100 mg/kg dose providedgreater than 90% tick efficacy through day 9 of the study.

EXAMPLE 3 Efficacy of Spinosad Administered per os to Dogs for theTreatment and Control of Fleas (Ctenocephalides felis)

Methods: Thirty-two (32) random source dogs of both sexes and variousages were used in the study to evaluate different dosages and physicalforms of spinosad and their impact on oral efficacy against fleas. Thedogs were housed individually in concrete-floored chain-link runs duringthe study period and were fed a commercial dry dog food ration with adlibitum access to water. The dogs were allocated to each of the 8treatment groups (4 dogs per group) based on their pre-treatment fleacounts from experimental infestations. Each dog received by mouth one ormore gelatin capsules containing technical spinosad in the differentphysical forms and dosages listed infra. They were dosed based on bodyweight on day 0. Each dog was fed approximately one-half can of moistdog food just prior to, and just after, receiving their individualgelatin capsules containing the specific spinosad formulation anddosage. Each dog was experimentally infested with ˜100 unfed adult fleason test days −1, 2, 6, 9, 13, 20,27 and 34. Comb counts for live adultfleas were conducted ˜24 hours following dosing or each of thesubsequent experimental infestations (i.e.—test days 1, 3, 7, 10, 14,21, 28 and 35).

Treatments:

Treatment Formulation Type & No. Oral Dose (mg/kg) Concentration 1 11.25Milled spinosad, tecnnical, in gelatin capsules 2 22.5 Milled spinosad,technical, in gelatin capsules 3 45 Milled spinosad, technical, ingelatin capsules 4 22.5 Amorphous spinosad, technical, in gelatincapsules 5 22.5 Unmilled spinosad, technical, in gelatin capsules 6Untreated control None

TABLE 4 Geometric Mean Percent Reduction in Live Adult Flea CountsCompared to Untreated Control Group in Dogs Treated Orally with SpinosadTreatment Days Post-Treatment No. 1 3 7 10 14 21 28 35 1 100.0 99.6 94.496.0 87.0 74.7 71.4 31.8 2 100.0 100.0 100.0 99.6 99.0 91.9 78.5 50.95 3100.0 100.0 100.0 100.0 99.8 99.5 98.9 94.2 4 100.0 100.0 100.0 100.0100.0 97.8 91.4 56.1 5 100.0 100.0 100.0 100.0 100.0 99.3 98.9 60.4

Summary: Orally administered spinosad provided excellent immediateknockdown efficacy (99.6 to 100% on days 1 & 3 post-treatment) and alsogood-to-excellent long term post-treatment residual control of fleas ondogs. The 45 mg/kg milled spinosad dose provided greater than 94% fleaefficacy through day 35 of the study. The lower dosages of milledspinosad provided shorter post-treatment residual control based on thedose. The adult flea efficacy of the ˜22.5 mg/kg spinosad dosages ofmilled (mean particle size of ˜5 microns), amorphous (non-crystalline),and unmilled (mixture of particles sizes greater than 5 microns with adistribution of up to ˜200 microns) were similar and not statisticallydifferent at day 28 post-treatment, indicating that particle size orcrystalline form does not impact the oral flea efficacy.

No adverse reactions were seen.

EXAMPLE 4 Efficacy of Spinosad Administered per os to Cats for theTreatment and Control of Fleas (Ctenocephalides felis)

Methods: Sixteen cats of both sexes and various ages were used in thestudy. The cats were housed individually in cages with litter boxes andwere fed a commercial dry cat food ration with ad libitum access towater. The cats were allocated to each of the 4 treatment groups (4 catsper group) based on their pre-treatment flea counts from experimentalinfestations. Each cat received by mouth one or two gelatin capsulescontaining milled technical spinosad powder and were dosed at either 0,12.5, 25 or 50 mg of spinosad per kg of body weight on day 0. Each catwas fed a small amount of moist cat food just prior to and just afterreceiving their individual gelatin capsules containing spinosad. Eachcat was experimentally infested with ˜100 unfed adult fleas on test days−1, 0 (8 hours), 2, 6, 9, 13, 20 and 27. Comb counts for live adultfleas were conducted ˜24 hours following dosing or each of thesubsequent experimental infestations (i.e.—test days 0 @ 8 hours, 1, 3,7, 10, 14, 21, and 28).

Table 5 summarizes the results of this study.

TABLE 5 Geometric Mean Percent Reduction in Live Adult Flea CountsCompared to Untreated Control Group in Cats Treated Orally with SpinosadSpinosad, Oral Hours/Days Post Treatment Dose (mg/kg) 8 hrs. 1 3 7 10 1421 28 12.5 94.6 100 100 96.7 85.0 92.2 68.2 36.1 25 97.4 100 100 98.197.1 95.4 83.1 69.7 50 97.0 100 100 97.5 97.8 97.9 90.9 74.4

Summary: Orally administered spinosad provided excellent immediateknockdown efficacy (94.6 to 100% at 8 hours and on days 1 & 3post-treatment) and also good to excellent long term post-treatmentresidual control of fleas on cats. The 50 mg/kg milled spinosad oraldose provided greater than 90% flea efficacy through day 21 of thestudy. The lower dosages of milled spinosad provided shorterpost-treatment residual control based on the dose.

Adverse reactions: one cat in the 25 mg/kg dose group and 2 cats in the50 mg/kg dose group vomited a small amount of food ˜1 hourpost-treatment. The cause is unknown.

EXAMPLE 5

The following is an example of a suitable tablet formulation:

Component Percent of Formulation by Weight Spinosad, technical, (90%)5.5 Microcrystalline cellulose 20.0 Compressible sugar 30.0Carboxymethyl cellulose, sodium 10.0 salt, crosslinked Magnesiumstearate 10.0 Silicon dioxide, colloidal 20.0 Tuna (fish) flavoring 4.5100.0

Each tablet contains 5% of the spinosyn component by weight.

EXAMPLE 6

The following is an example of a suitable liquid formulation:

Component Percent of Formulation by Weight Spinosad, technical, (90%)5.5 Water soluble dye 1.0 Methyl cellulose 6.0 Water 83.0 Fish flavoringagent 4.5 100.0

This formulation contains 5% of the spinosyn component by weight.

What is claimed is:
 1. A single-dose oral formulation for controlling an ectoparasite infestation on a dog or cat comprising an ectoparasiticidal amount of spinosad, or a physiologically acceptable derivative or salt thereof, and a physiologically acceptable carrier in a systemically effective oral dosage form selected from tablet, capsule or liquid suitable for administration once every at least 7 days at a dose of 10 to 100 mg of spinosad per kg of body weight.
 2. A formulation of claim 1 wherein the dosage form is a tablet and the amount of the spinosad is from 1 to 75 percent by weigth of the tablet.
 3. A formulation of claim 1 which is administered once every two weeks.
 4. A formulation of claim 1 which is administered once every 30 days.
 5. A single-dose oral formulation for controlling an ectoparasite infestation on a dog or cat comprising an ectoparasiticidal amount of spinosad, or a physiologically acceptable derivative or salt thereof, and a physiologically acceptable carrier in a systemically effective chewable treat oral dosage form suitable for administration once every at least 7 days at a dose of 10 to 100 mg of spinosad per kg of body weight.
 6. A formulation of claim 5 which is administered once every two weeks.
 7. A formulation of claim 5 which is administered once every 30 days. 